End-stage renal disease (ESRD) introduces physical, psychological, social, emotional and spiritual challenges into patients’ lives. Spirituality has been found to contribute to improved health outcomes, mainly in the areas of quality of life (QOL) and well-being. No studies exist to explore the influences of spirituality on the health outcomes and general well-being in patients with end-stage renal disease receiving haemodialysis (HD) treatment in Scotland. This study was therefore carried out to examine and explore spirituality in the day-to-day lives of patients with ESRD receiving HD treatment and how it may influence their health outcomes and, in particular, QOL and general well-being. The study described in this thesis employed a sequential mixed method approach over two stages: quantitative and qualitative. Following ethical approval, a cross-sectional survey was conducted with 72 patients from 11 dialysis units recruited from four Health Boards in Scotland. The participants in the study were regular patients attending the dialysis units three times per week. Data on patients’ quality of life, general well-being, and spirituality were collected using self-administered questionnaires including demographic information: the Short Form Medical Outcome Study Questionnaire (SF-36v2), the General Health Questionnaire, and the Spiritual Well-Being Questionnaire. The data were analysed using the Predictive Analytics Software for Windows. The findings highlighted that patients’ quality of life was markedly lower than the United Kingdom general population average norms of 50. Increasing age was associated with better mental health but worse physical health. The survey also found that there were no significant associations between spirituality and patients’ quality of life and general well-being. However, it was considered important to complement and enrich the survey findings by gaining a deeper understanding of the influences of spirituality on patients’ health outcomes and general well-being by carrying out the qualitative component of the study. Qualitative data were collected using semi-structured interviews with a subsample of 21 patients from those who participated in the survey. A thematic approach using Framework Analysis informed the qualitative data analysis. Four main themes emerged from the qualitative interviews: ‘Emotional and Psychological Turmoil’, ‘Life is Restricted’, ‘Spirituality’ and ‘Other Coping Strategies’. The findings from the interviews confirmed that patients’ quality of life might be affected because of the physical challenges such as unremitting fatigue, disease unpredictability, or being tied down to a dialysis machine, or the emotional and psychological challenges imposed by the disease into their lives such as wholesale changes, dialysis as a forced choice and having a sense of indebtedness. The findings also revealed that spirituality was an important coping strategy for the majority of participants who took part in the qualitative component (n=16). Different meanings of spirituality were identified including connection with God or Supernatural Being, connection with the self, others and nature/environment. Spirituality encouraged participants to accept their disease and offered them a sense of protection, instilled hope in them and helped them to maintain a positive attitude to carry on with their daily lives, which may have had a positive influence on their health outcomes and general well-being. The findings also revealed that humour was another coping strategy that helped to diffuse stress and anxiety for some participants and encouraged them to carry on with their lives. The findings from this study contribute knowledge to increase our understanding of the influence of spirituality on the health outcomes and general well-being of patients with end-stage renal disease currently receiving haemodialysis treatment. Based on the findings from this thesis, recommendations are made for clinical practice, patient and nurse education and for future research.

L’insuffisance rénale chronique (IRC) terminale est une situation peu fréquente chez l’enfant mais a des conséquences importantes sur la survie et la qualité de vie. De nos jours, la majorité des enfants en IRC terminale en Europe vont recevoir une greffe de rein après un traitement de suppléance par dialyse ou de manière préemptive après un traitement conservateur de l’insuffisance rénale. Les objectifs de cette thèse sont de décrire l’épidémiologie de l’IRC chez l’enfant, d’évaluer les différences de pratiques et d’accès à la greffe rénale entre pays Européens, et d’investiguer le devenir clinique après transplantation, notamment la survie du greffon, la croissance, et la récidive de la maladie initiale sur le greffon. Premièrement, une revue de littérature sur l’épidémiologie de l’IRC chez l’enfant a été réalisée. Deuxièmement, nous avons mis en évidence par une enquête d’importantes variations de pratiques, de politiques d’allocation des greffons rénaux et d’accès à la greffe rénale pédiatrique à travers l’Europe. Des facteurs tels que le taux de greffe avec donneur vivant, la priorité nationale donnée aux enfants pour les donneurs décédés, ou un indicateur de richesse tel que le produit intérieur brut étaient associés à un meilleur accès à la greffe par pays. Troisièmement, l’étude du devenir après greffe par des études observationnelles a montré une amélioration de de la survie des greffons et de la taille à l’âge adulte après IRC terminale dans l’enfance. En utilisant l’oxalose comme exemple de maladie à haut risque de révidive, nous avons trouvé que le pronostic des enfants atteints d’oxalose en IRCT s’est amélioré au cours du temps. Il a été possible de déterminer quelles pratiques cliniques sont associées avec le meilleur devenir. L’ensemble de ces résultats suggère une augmentation de la prévalence et une meilleure prise en charge des enfants transplantés du rein en Europe. / Although end-stage renal disease (ESRD) is a rare condition in children, it has major consequences on their survival and quality of life. Most children with ESRD in Europe nowadays receive a renal transplant after variable periods of renal replacement therapy (RRT) with dialysis, or preemptively after conservative treatment of chronic kidney disease (CKD). The objectives of this thesis are to describe the epidemiology of CKD in children, to evaluate the differences of practices and access to transplant in Europe, and to investigate post transplant outcomes including graft survival, final height and disease recurrence. First, a literature review of the available data on pediatric CKD epidemiology was performed. Second, we analyzed the differences in transplantation practices, kidney allocation policies and access to transplantation between European countries in a survey study. Living donor transplant rate, national priority given to children, and an economic indicator like gross domestic product were found to be associated with a better access to transplantation by country. Third, we assessed post transplantation outcomes in longitudinal observational studies, including data from the European registry. We showed an improvement of graft survival and of adult height after childhood RRT over the years. Using oxalosis as an example of a rare disease with high risk of recurrence, we also found that the prognosis on RRT of children with such a disease improved over time. Some practices associated with better outcomes could be identified. Overall, our findings suggest an increasing prevalence and progress in the management of pediatric kidney transplant recipients in Europe.

Τα μέχρι σήμερα βιβλιογραφικά δεδομένα συνηγορούν υπέρ της ύπαρξης σύνδεσης μεταξύ της γονεϊκής νόσου και αυξημένης επίπτωσης συναισθηματικών και συμπεριφοριστικών προβλημάτων στα παιδιά Ωστόσο, στην Ελλάδα δεν υπάρχουν καθόλου βιβλιογραφικά δεδομένα, σχετικά με την σύνδεση της Χρόνιας Νεφρικής Ανεπάρκειας και ειδικότερα της θεραπείας ενδονοσοκομειακής αιμοκάθαρσης (ΑΜΚ) στους γονείς και της πιθανής εμφάνισης ψυχοπαθολογίας στα τέκνα αυτών. Εστία αυτής της μελέτης αποτέλεσε η συσχέτιση της ΧΝΑ και της ΑΜΚ στον γονέα με συγκεκριμένες διαγνωστικές κατηγορίες ή υποκατηγορίες Ψυχικών Διαταραχών στα παιδιά των ασθενών αυτών. Μελετήθηκαν προοπτικά 53 παιδιά, των οποίων ο πατέρας ή η μητέρα υποβαλλόταν σε ΑΜΚ, ηλικίας 6-21 ετών, με την χρήση των Ερωτηματολογίων της Achenbach για γονείς καθώς και με τη χρήση της Ημιδομημένης Ψυχιατρικής Διαγνωστικής Συνέντευξης για Παιδιά και Εφήβους K-SADS-PL. Επίσης εξετάσθηκε η ψυχική υγεία των ασθενών γονέων, με την χρήση της διαγνωστικής συνέντευξης SCID-I και SCID-II και των υγιών γονέων με την χρήση των ερωτηματολογίων ΗΑΜ-D και HAM-A. Διαπιστώθηκαν στατιστικά σημαντικές διαφορές σε όλες τις ομάδες συμπεριφορών της κλίμακας CBCL και στις δυο ηλικιακές ομάδες (6-18 & 18-21). Επίσης αναδείχθηκε ότι τα παιδιά της πειραματικής ομάδας παρουσίαζαν υψηλότερα ποσοστά ψυχοπαθολογίας, συγκριτικά με τους μάρτυρες ως προς την ψυχική υγεία των ασθενών γονέων ευρέθη ότι το 48.3% συμπλήρωναν τα κριτήρια για μια τουλάχιστον Ψυχική Διαταραχή, ενώ το αντίστοιχο ποσοστό στους μάρτυρες ήταν 20.7% (ΟR=6.7, 95% CI 2.0-28.7). Η μέση τιμή της βαθμολογίας που καταγράφηκε για την κατάθλιψη των συζύγων ασθενών ήταν 15.31 (SD=11.7) ενώ των συζύγων-μαρτύρων ήταν 3.19 (SD=3.65), διαφορά η οποία είναι στατιστικώς σημαντική (p<0.001). Τα υπό μελέτη παιδιά εμφανίζουν μεγαλύτερη ψυχοπαθολογία συγκριτικά με τους μάρτυρες, με επικρατέστερη της διαταραχή «Ειδική Φοβία» αλλά και την «Κατάθλιψη» και «Διαταραχή Διαγωγής». Επίσης, παρουσιάζουν περισσότερα συμπεριφορικά προβλήματα σε όλες τις επιμέρους Συμπεριφορές της κλίμακας CBCL, χαμηλότερες τιμές στο προφίλ ικανοτήτων, ενώ στα μεγαλύτερα σε ηλικία παιδιά ανεβρέθηκαν περισσότερα συναισθηματικά προβλήματα. Οι ασθενείς γονείς εμφανίζουν συντριπτικά υψηλότερα ποσοστά στις διαταραχές Διάθεσης, ενώ και στους υγιείς γονείς αναδείχτηκαν πολύ αυξημένα επίπεδα αγχώδους και καταθλιπτικής συμπτωματολογίας. Απαραίτητη είναι η διεξαγωγή προοπτικών μελετών, που θα αναδείξουν την ψυχοκοινωνική εξέλιξη των παιδιών αυτών στο χρόνο. / Bibliographic data up to today speak in favour of the existence of a strong connection between the parental illness and increased sentimental and behaviouristic problems in the children. However, in Greece no data exists. The aim of the present study was to explore the possible psychological impact on the children, who have a parent undergoing in-centre hemodialysis (HD) in Greece. We investigated 53 children, aged 6-21 years old, living at home, whose one parent was undergoing in-centre haemodialysis. The parents were recruited from 4 different haemodialysis centres in Southern Greece. Control subjects were matched with the study children for age, sex, place of residence, socioeconomic status and parental educational level. The data collection was carried out by filling the Child Behavior Checklist (CBCL) and the Adult Behavior Checklist (ABCL), with reports of the ill parent describing specific behavioral and emotional problems of the child, when the psychopathology of the children and their ill parents was studied according to DSM-IV criteria. Children of parents undergoing haemodialysis scored statistically significantly higher than the children in the control group (p<0.01, Wilcoxon signed-ranks test for paired data) on all aspects of trends in behavior (internalizing, externalizing, neither internalizing nor internalizing) on the CBCL and the ABCL scale. We found that this result would remain, even if it was tested with respect to sex (male/female) and age (6-18, 18-21). On the internalizing composite scale females aged 18-21 scored higher than males of same age. Also psychiatric disorders were by 1.8 -fold more frequent in the children of HD parents than in the control children. Ill parents suffered more from a psychiatric disorder (65.5%) in comparison with their controls (20%). The results of this study suggest that parental illness affects negatively the mental health of their dependent offspring aged 6-21 years old. Older children and mainly females seem to be more prone to depressive symptoms. Ill parents suffer greatly from psychiatric disorders and the most common is depression. Also it seems that parental mental health (both in the ill and the healthy parent) influence the mental health of the children. Essential is the conduct of prospective studies that will elect the psychosocial development of this population.

Depression is common in haemodialysis (HD) patients and is often unrecognised and undertreated, though associated with excess morbidity and mortality. Diagnosis is challenging due to symptom overlap with kidney failure, with fatigue being the most common overlapping symptom. Research on the effectiveness of antidepressant medication in this setting is sparse. A recent systematic review advocated well-designed Randomised Controlled Trials (RCTs) in this setting. The studies reported in this thesis had a number of aims. The main aim was to undertake a multicentre feasibility randomised, double blind, placebo-controlled trial of sertraline in patients on HD with Major Depressive Disorder (MDD). To identify suitable patients for this, a screening phase was required, which also allowed determination of the prevalence of depression in this setting and of the relative effectiveness of screening tools Patient Health Questionnaire-2 (PHQ-2), Patient Health Questionnaire-9 (PHQ-9), and Beck Depression Inventory-II (BDI-II). It also allowed examination of the relationships of fatigue in this setting (assessed mainly by the Multidimensional Fatigue Inventory (MFI), including those with a diagnosis, and management of depression. The finding, during screening, that a large proportion of the HD cohort was already on antidepressant treatment, presented the opportunity to study 'real-life' practice patterns in the management of antidepressant treatment in this setting. Recruitment into the RCT was difficult. 1,355 patients in five HD centres were considered for screening, but 243 of these were excluded, mainly because of their inability to read and understand English. Of the remaining 1,110 patients, 709 consented to screening. 231 of these screened positive for high depression symptoms but 130 were not considered for the trial phase, mainly because of concurrent treatment for depression (68 patients), and other contraindicated conditions and medication. In addition, 38 patients declined to take part in the psychiatric interview necessary for diagnosis of MDD. Of the 63 who underwent the diagnostic interview, 37 (58.7%) were diagnosed with MDD and 30 consented to enter the RCT and were randomised into sertraline or placebo groups. This was half of the anticipated recruitment into the RCT. Twenty-one patients (70%) completed the six-month study, eight of 15 in the sertraline group and 13 of 15 in the placebo group (p < 0.05). Drop out was mainly due to adverse or serious adverse events. Depression scores (BDI-II and Montgomery-Åsberg Depression Rating Scale (MADRS)) improved significantly in both the sertraline and placebo groups over six months but there were no significant differences between the treatment groups. There was a slight suggestion of more rapid improvement over the first two months on sertraline, but this was not significant. Fatigue scores were high in all sub-domains - with only a weak relationship with age and comorbidity. Mental fatigue was the strongest independent predictor of high depressive symptoms (BDI-II ≥16, PHQ-9 ≥8), while physical fatigue had the strongest relationship with dialysis recovery time, and survival. Distinguishing between these components of fatigue may have a role in refining the diagnosis and management of MDD. Forty-one of the 76 patients on antidepressant medication at screening were followed up for a mean of 14±5 months. Ten different antidepressant agents were being taken - the most common being Citalopram (39%). Most had been prescribed by GPs. Two-thirds of patients either deteriorated or failed to improve in terms of BDI-II scores during follow-up, many of whom had had no adjustment of medication during this time. Diagnostic evaluation at follow-up showed 37% to be suffering from current or recurrent major depressive episodes (MDE), 48% to have evidence of past MDE, and 15% to have no evidence of ever having been depressed. These empirical studies confirm that depression is very common in HD patients. Its diagnosis is complicated due to symptom overlap with the uraemic syndrome. Fatigue seems to be a key area of overlap with symptoms of depression with a complex relationship. There was no obvious benefit from antidepressants in this feasibility RCT and there was a high drop-out rate due to adverse events, particularly in the sertraline group. These findings raise concerns about the benefits and risks of antidepressants in patients on HD. Current practice patterns may be subjecting patients to substantial risk for little or no benefit. Identifying whether antidepressant medication is effective in this context is a major clinical need, hence the requirement for a definitive study. There is no doubt that to undertake a definitive study would pose considerable recruitment challenges. The findings presented here emphasise the importance of finding ways to overcome these challenges that might include efforts to incorporate patients already taking antidepressants.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-06-19T12:43:50Z No. of bitstreams: 1 felipemartinsdovalle.pdf: 1212367 bytes, checksum: 1eb080fe9bb9c5ae3bdedfa118be339b (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-29T12:23:35Z (GMT) No. of bitstreams: 1 felipemartinsdovalle.pdf: 1212367 bytes, checksum: 1eb080fe9bb9c5ae3bdedfa118be339b (MD5) / Made available in DSpace on 2017-06-29T12:23:35Z (GMT). No. of bitstreams: 1 felipemartinsdovalle.pdf: 1212367 bytes, checksum: 1eb080fe9bb9c5ae3bdedfa118be339b (MD5) Previous issue date: 2017-02-22 / Introdução: O sedentarismo é altamente prevalente e aumenta a taxa de mortalidade por todas as causa em pacientes com doença renal crônica (DRC) em hemodiálise (HD). Em contraste, um estilo de vida mais ativo está associado a ganhos para esses pacientes. Assim, investigamos os efeitos do treinamento resistido intradialítico e supervisionado no nível de atividade física diária (NAFD), na capacidade funcional (CF), na qualidade de vida (QV) e na força muscular (FM) de pacientes com DRC em HD. Métodos: Vinte e quatro pacientes com DRC (54,2 ± 13,5 anos) em HD (6,0 ± 5,7 anos) foram randomizados para treinamento resistido de moderada intensidade ou controle. O treinamento resistido foi realizado durante as duas primeiras horas das sessões de HD, três vezes por semana, durante três meses. O NAFD foi avaliado por um acelerômetro pelo tempo gasto em diferentes atividades da vida diária (caminhando, em pé, sentado e deitado) e o número de passos. O acelerômetro foi utilizado por sete dias consecutivos (três dias dialíticos e quatro dias de não dialíticos). A CF, a QV e a FM foram avaliadas pelo teste de caminhada de seis minutos (TC6M), questionário SF-36 e pelo teste de contração isométrica voluntária máxima (CIVM), respectivamente. Os valores foram representados em deltas (pós-tratamento menos pré-tratamento). Resultados: Após três meses de treinamento resistido, não foi encontrada diferença significativa no tempo de caminhada (-1,2 ± 18,3 vs. -9,2 ± 13,1 min/dia), no tempo em pé (-10,2 ± 28,6 vs. ± 20,1 min/dia), no tempo sentado (20,8 ± 58,9 vs. -30,0 ± 53,0 min/dia), no tempo deitado (-9,3 ± 57,9 vs. 34,6 ± 54,0 min/dia) e no número de passos [-147 (1834) vs. -454 (2066)] entre os grupos exercício e controle, respectivamente. A distância percorrida no TC6M aumentou significativamente no grupo de treinamento em relação ao grupo controle (48,8 ± 35,9 vs. 6,9 ± 45,9 m, p=0,04). Não foi encontrada diferença significativa na FM (3,4 ± 7,2 vs. 0,5 ± 7,3 Kgf) entre os grupos treinamento e controle, respectivamente. Três domínios do SF-36 apresentaram aumento significativo no grupo treinamento em relação ao controle, respectivamente [capacidade funcional = 13,7 ± 9,9 vs. -12,5 ± 16,7, p=0,003; limitação por aspectos físicos = 0,0 (0,0) vs. -50,0 (93,7), p=0,03; estado geral da saúde = 6,6 ± 14,1 vs. -10,4 ± 21,4, p=0,01). O treinamento resistido intradialítico foi realizado com segurança por todos os participantes. Conclusão: O presente estudo demonstrou que o NAFD não foi modificado após três meses de treinamento resistido intradialítico em pacientes com DRC submetidos à HD. No entanto, esse programa de exercícios foi capaz de aumentar a CF e alguns domínios da QV nesses pacientes. / Background: Physical inactivity is highly prevalent and increases all causes of mortality in end-stage renal disease (ESRD) patients on hemodialysis (HD). In contrast, a more active lifestyle is associated with better outcomes in these patients. We therefore investigated the effects of supervised intradialytic resistance training on physical activities in daily life, physical capacity, quality of life and muscle strength in ESRD patients. Methods: Twenty four ESRD patients (54.2 ± 13.5 years) under HD (6.0 ± 5.7 years) were randomly assigned to either 3-month moderate-intensity resistance training or a control period. Resistance training was performed during the first two hours of HD sessions, three times a week, for three months. Physical activities in daily life was evaluated using an accelerometer regarding the time spent in different activities and positions of daily life (walking, standing, sitting and lying down), and the number of steps taken. The accelerometer was used for seven consecutive days (three dialysis days and four nondialysis days). Physical capacity, quality of life and muscle strength were evaluated by six-minute walking test (6MWT), SF-36 questionnaire and maximum voluntary isometric contraction test, respectively. The values were expressed as delta (post-pre treatment). Results: After three months of training, we didn’t find significant difference in walking time (-1.2 ± 18.3 vs. -9.2 ± 13.1 min/day), standing time (-10.2 ± 28.6 vs. 3.2 ± 20.1 min/day), sitting time (20.8 ± 58.9 vs. -30.0 ± 53.0 min/day), lying down time (-9.3 ± 57.9 vs. 34.6 ± 54.0 min/day) and number of steps taken [-147 (1834) vs. -454 (2066)] in training and control groups, respectively. The 6MWT distance increased significantly in training group when compared with control group (48.8 ± 35.9 vs. 6.9 ± 45.9 m, p=0.04). No significant difference was found in muscle strength (3.4 ± 7.2 vs. 0.5 ± 7.3 Kgf) in training and control groups, respectively. Three domains of the SF-36 showed significant increase in training group when compared with control group, respectively (physical functioning = 13.7 ± 9.9 vs. -12.5 ± 16.7, p=0.003; role physical = 0.0 (0.0) vs. -50.0 (93.7), p=0.03; general health = 6.6 ± 14.1 vs. -10.4 ± 21.4, p=0.01). Intradialytic resistance training was safely performed by all participants. Conclusions: The present study showed that daily life activities were not modified after three months of intradialytic resistance training in HD patients. However, the exercise program was able to increase the physical capacity and some domains quality of life in these patients.

Abstract The aim of this work was to evaluate the outcome of childhood Henoch-Schönlein purpura (HSP), the effectiveness of Cyclosporine A (CyA) for treating severe HSP nephritis (HSN), and more particularly the possibility for influencing the course of HSP disease by early prednisone treatment. A total of 47 adults who had had childhood HSP were evaluated after a mean of 24.1 years (16.4–35.6). The outcome was highly dependent on the renal symptoms at onset, since 7 out of 20 adults (20%) who had severe renal symptoms at onset had renal impairment as adults, compared with 2 out of 27 (7%) with mild or no renal symptoms at onset (relative risk 4.7; 95% CI 1.3–18.7). 70% of pregnancies in women after childhood HSN were complicated by hypertension or proteinuria. The annual incidence of HSN with nephrotic-range proteinuria was 2 per million children under 15 years. After a mean follow-up of 4.6 years, only three patients out of 19 were in complete remission. Kidney biopsy did not predict the outcome in these patients. CyA seemed to be promising for the treatment of severe HSN with nephrotic-range proteinuria, since four out of seven patients treated with CyA achieved stable remission and three had preserved their renal function after a mean follow-up of 6.0 years. Treatment at an early stage in the disease was associated with stable remission. The efficacy of early prednisone treatment was evaluated in a randomized double-blind trial involving 171 patients (84 prednisone, 87 placebo). Prednisone, given at a dose of 1 mg/kg/day for 2 weeks, with weaning over the next two weeks, was effective in reducing the intensity of abdominal pain (pain score 2.5 vs. 4.8; t-test p = 0.029) and shortening its duration (1.5 days vs. 2.7 days; t-test p = 0.028) compared with the placebo. The mean scores for joint pain were lower in the prednisone group (4.6 vs. 7.3; t-test p = 0.030) and the improvement from joint symptoms was faster (log rank p = 0.007). Prednisone did not prevent the development of renal symptoms but it was effective in treating them, since renal symptoms resolved in 61% of the prednisone patients after treatment compared with 34% of the placebo patients (difference 27%, 95% CI 3–47%, p = 0.024). Prednisone was most effective for children aged 6 or more with renal symptoms at onset, since only two patients needed to be treated in order to save one from renal involvement (95% CI's for NNT 2–6). The long-term outcome of HSP is dependent on renal symptoms. Severe renal symptoms indicate early immunosuppressive treatment for HSN, and patients with renal involvement at the acute phase need long-term follow-up, especially women during and after pregnancy. Early treatment with prednisone is effective in reducing the abdominal and joint symptoms involved in HSP and is also effective in altering, but not preventing, the course of renal involvement. / Tiivistelmä Väitöskirjatyön tarkoituksena oli selvittää lapsuusiän Henoch-Schönleinin purppuran (HSP) pitkäaikaisennustetta, Siklosporiini-A:n (CyA) tehoa vaikean HSP-nefriitin hoidossa ja tutkia varhain aloitetun prednisonihoidon hyötyä HSP-taudin oireisiin. HSP:n pitkäaikaisennustetta selvitettiin tarkastamalla 47:n lapsena HSP-taudin sairastaneen aikuisen terveystilanne keskimäärin 24.1 vuoden (16.4-35.6) seuranta-ajan jälkeen. HSP-taudin ennuste oli vahvasti riippuvainen munuaisoireen vaikeusasteesta: 20 % niistä, joilla taudin alussa oli vaikeat munuaisoireet, kärsi vielä aikuisiällä munuaisoireista; vastaava luku munuaisoireettomilla ja niillä, joilla oli ollut vain lievää veri- tai valkuaisvirtsaisuutta, oli 7 %, (RR 4.7; 95 % CI 1.3–18.7). Raskauskomplikaatiot olivat yleisiä lapsuusiällä HSP-taudin sairastaneilla naisilla, sillä 70 % raskauksista komplisoi korkea verenpaine tai valkuaisvirtsaisuus. Vuosittain 2 lasta miljoonasta sairastuu vaikeaan nefroottistasoiseen HSP-nefriittiin Suomessa. Vain kolme nefroottistasoiseen HSP-nefriittiin sairastuneesta 19 lapsesta oli 4.6 vuoden seurannan jälkeen parantunut oireettomaksi. Ensimmäisen munuaisbiopsian vaikeusaste ei ennakoinut selviytymistä. CyA näytti olevan lupaavan tehokas lääke vaikean HSP-nefriitin hoidossa, sillä neljä seitsemästä CyA-hoitoa saaneesta lapsesta, oli oireeton 6.0 vuoden seurannan jälkeen. Mitä aikaisemmin vaikean nefriitin hoito oli aloitettu, sen parempi hoitotulos oli. Varhain aloitetun prednisonihoidon hyötyä HSP-taudin oireisiin selvitettiin satunnaistetulla kaksoissokkotutkimuksella, johon satunnaistettiin 171 lasta (84 prednisoni, 87 lumelääke) saamaan joko prednisonia 1 mg/kg/päivä 2 viikon ajan tai lumelääkettä. Prednisoni vähensi tehokkaasti vatsa- ja nivelkipuja ja se lyhensi merkitsevästi myös niiden kestoa. Prednisoni ei estänyt munuaisoireen kehittymistä lapselle, mutta niiltä, joille se kehittyi, oireet hävisivät merkitsevästi nopeammin lumelääkitykseen verrattuna (61 % versus 34 %, 95 % CI 3–47 %, p = 0.024). Kaikkein tehokkainta prednisoni oli yli 6 vuotiaille lapsille, joilla oli munuaisoire heti taudin alussa (NNT 2, 95 % CI 2–6). Tutkimuksen perusteella voidaan sanoa, että lapsuusiällä HSP-nefriitin sairastaneet lapset tarvitsevat seurantaa aikuisiällä, erityisesti naiset raskauden aikana. HSP-nefriitin varhainen hoitaminen on tärkeää. Varhainen prednisonihoito ei estä munuaisoiretta, mutta hoitaa jo kehittynyttä nefriittiä ja vähentää vatsa- ja nivelkipuja tehokkaasti.

Les objectifs sont d’évaluer l’efficience (survie, qualité de vie et le coût) des deux techniques de dialyse de rechercher les déterminants qui orientent le choix vers l’une ou l’autre des techniques de dialyse et d’évaluer le parcours de soins des patients en dialyse. La première partie de ce travail de thèse à analyser les données de la région PACA issues du registre REIN. Cette analyse est descriptive et porte sur le profil des patients démarrent un traitement en dialyse (HD et DP). Une analyse de survie a été réalisée selon la technique de dialyse initiale et selon le parcours de soins. Dans une seconde partie, le coût et sur la qualité de vie ont été évalués selon les différentes techniques de dialyse afin d’évaluer l’efficience de ces modalités à partir des données recueillies dans un PHRC régional. Dans une troisième partie, les facteurs liés au choix initial de la technique de dialyse, DP ou HD ont été recherchés. Ce travail a fait l’objet d’une étude ciblée auprès de patients et de néphrologues au sein de 4 structures de dialyse. La survie et la qualité de vie des patients sont similaires entre HD et DP. Le changement de technique, de la DP vers l'HD, a un impact positif sur la survie. La DP est moins coûteuse que l’HD. Les contre-indications médicales à la DP ne concernaient que 26,7% des patients inclus. En absence de contre-indications, la préférence du patient et les pratiques des professionnelles (information et pratiques de centre) sont les deux principaux facteurs liés au choix initial de la technique de dialyse, notamment par la DP. Une meilleure information pourrait contribuer à augmenter le choix de la DP. / The objectives of this work were to assess and compare the efficiency (survival, quality of life and cost) of patients initially treated with peritoneal dialysis (PD) or hemodialysis (HD), to search determinants that guide the initial choice towards either dialysis techniques and to assess the trajectory between dialysis modalities. The first part of this thesis was to analyze the database, from the PACA region (2004 – 2014), issue from the French REIN registry. This analysis was descriptive and focused to analyze main characteristics and outcome (survival) of dialysis patients (initial dialysis and switching) and to identify risk factors. The second part of this thesis was to measure and compare dialysis patient quality of life and health’s care costs between dialysis modalities (HD and PD). Database was issued from PHRC. The third part was to search the factors related to the initial choice of dialysis technique, PD or HD. This work was the subject of a targeted survey of patients and neurologists in a dialysis structure. The survival and the quality of life were similar between hemodialysis and peritoneal dialysis. Switching to HD may improve positively the survival compared to those who remained on PD, whereas, switching to PD was not. The DP is less expensive than HD. Medical contraindications to the PD were for 26.7%. In the absence of contraindications, patient preference and professional practices (information and practical center) are the two main factors related to the initial choice of dialysis technique, in particular to choice of PD. Better information could help to increase the choice of DP

The concept of health-related quality of life (HRQoL) had been used as a patient reported outcome measure in healthcare settings. It has been conceptualised and measured using validated instruments in the Western scientific community. However, in the Saudi literature, the true meaning of this concept is still lacking. The aim of this study is to explore the gap in literature and define the concept of HRQoL, identify its key domains and conceptualise it as perceived specifically by patients with renal failure and undergoing haemodialysis in Saudi Arabia. This PhD included two strands, an empirical qualitative study and a critical analysis of the HRQoL concept and its measurement in the Western as well as the Saudi literature. Using qualitative research methods, the empirical study was conducted in one centre in the Eastern Region of Saudi Arabia. Twenty two In-depth qualitative interviews were conducted in the Arabic language, recorded, transcribed and translated into English. Thematic analysis was performed to analyse the data as the transcripts were coded, the categories identified and the themes generated. The conceptual analysis of HRQoL was carried out after the review of the Western literature on the quality of life (QoL) conceptual models and the measuring instruments used in renal literature. Systematic review of the Saudi HRQoL literature was performed as well to understand the meaning and methods of measurement of the concept of HRQoL. The conceptual analysis of HRQoL revealed that the concept is poorly defined in the Saudi literature; its measurement was based on instruments that are not culturally-adapted. Hence the findings are subjected to questions of validity and reliability. The QoL conceptual models have been developing in the Western literature as well as measuring instruments for patients with renal failure. However, the adoption of these models or instruments is critical due to social, cultural and religious variations between Saudi Arabia and the Western societies. Seven themes defining HRQoL emerged from the qualitative data; these reflected the subjectivity of the concept. The domains of HRQoL were the physiological, social, psychological, religious and vocational domains. Each of those domains was defined by determinants that affect other domains and the overall HRQoL. These were synthesised into a single definition, which incorporated all five domains. A model of HRQoL of patients undergoing haemodialysis in Saudi Arabia was developed explaining the relationship between the key domains and HRQoL. Healthcare services were discussed as a factor that affects the health status of patients and plays an indirect role in the life quality of this patient group. Hence it was considered as a factor rather than a domain. This study, including the conceptual analysis and the empirical study, illustrates that the concept of HRQoL is highly individual and is affected by the views of individuals living in a specific culture. Additionally, it is affected by the social, cultural and religious backgrounds of those individuals. The conceptualisation of HRQoL in this study was almost similar to the Western conceptualisation, however, the relationships between the key domains of HRQoL and their determinants differed. The social and religious domains were highly influenced by the Arabic culture and the Islamic religion. HRQoL in patients with ESRD in the Eastern Region of Saudi Arabia has a different meaning and conceptualisation from that seen in comparable Western literature. The assessment of HRQoL of patients with renal failure and on haemodialysis in Saudi Arabia requires a culturally-adapted instrument. This would ensure valid and reliable results that could be used in decision-making and the planning of care.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-18T21:07:30Z No. of bitstreams: 1 Anderson Soares Silva.pdf: 1994888 bytes, checksum: 0d17fc79f295d4a5c192dd3d298390d0 (MD5) / Made available in DSpace on 2018-07-18T21:07:30Z (GMT). No. of bitstreams: 1 Anderson Soares Silva.pdf: 1994888 bytes, checksum: 0d17fc79f295d4a5c192dd3d298390d0 (MD5) Previous issue date: 2017-10-27 / Introduction: Currently, end stage renal disease (ESRD) is one of the most serious public health problems, becoming a global epidemic. It is also known that the amount of nocturnal rostral fluid displacement from the lower limbs is related to increased neck circumference and the severity of obstructive sleep apnea (OSA) in patients with end-stage renal disease. Method: A cross-sectional study was carried out to verify the degree of upper airway collapsibility in patients with ESRD. Negative expiratory pressure and baseline nocturnal polygraphy will be performed before and after the hemodialysis session. Results: There was a significant difference in pre and post hemodialysis in the various apnea / hypopnea index, neck circumference, waist circumference, percentage of exhaled flow at the time of 0.2 seconds (V0.2) sitting and lying down. The VO, 2 sitting pre-hemodialysis presented a correlation with the pre-AHI (p = 0.047, r = -0.953) and post hemodialysis (p = 0.010; r = -0.990). In addition, V0.2 after hemodialysis showed a correlation with AHI after hemodialysis (p = 0.029; r = -0.971). Discussion: The NEP test was promising for clinical use, since it has a rapid application and presents information relevant to the collapse of the airway of patients with suspected OSA. / Introdução: Atualmente, a doença renal em estagio terminal (DRET) é um dos mais sérios problemas de saúde pública, tornando-se uma epidemia global. Sabe-se também que a quantidade de deslocamento do fluido rostral durante a noite, proveniente dos membros inferiores, está relacionada ao aumento da circunferência do pescoço e a gravidade da apnéia obstrutiva do sono (AOS) em pacientes com doença renal em estágio final. Método: Foi proposto um estudo clinico transversal com o objetivo de verificar o grau de colapsabilidade da via aérea superior em pacientes com DRET. Foi realizado o teste da pressão expiratória negativa (NEP) e a poligrafia basal noturna domiciliar antes e após a sessão de hemodiálise. Resultados: Houve diferença significativa em pré e pós hemodiálise nas váriaveis índice de apneia / hipopneia, circunferência de pescoço, circunferência de cintura, porcentagem de fluxo exalada no momento de 0,2 segundos (V0,2) sentado e deitado. O VO,2 sentado pré hemodiálise apresentou correlaçao com o IAH pré (p= 0,047; r= -0,953) e pós hemodiálise (p=0,010; r= -0,990). Além disso, o V0,2 pós hemodiálise apresentou correlação com IAH pós hemodiálise (p=0,029; r= -0,971). Discussão: O teste da NEP foi promissor para o uso clínico, uma vez que ele possui uma aplicação rápida e apresenta informações relevantes para a colapso da via aérea dos pacientes com suspeita de AOS.

El plan de negocio pertenece al sector salud y consiste en la creación del primer Centro especializado en Hemodiálisis con terapia de la risa en la ciudad de Lima. En la región de Lima existe una demanda insatisfecha de pacientes con Enfermedad Renal Crónica Terminal del Análisis de la situación renal en el Perú (2015) se puede concluir que existe un exceso de demanda de pacientes en EsSalud, con un sobredimensionamiento de un 33,9% y un déficit de cobertura en el Ministerio de Salud en un 79%. Es importante detallar que se han visto estudios sobre los beneficios de la terapia de la risa en pacientes con Enfermedades Crónicas Terminales y familiares respecto a su calidad de vida. Por ello, se propone la creación del primer Centro especializado en Hemodiálisis con terapia de la risa en la ciudad de Lima llamado “Centro de Hemodiálisis NefroClown S.A.”. Siendo el slogan de nuestro centro “…Donde la salud comienza con una sonrisa”. Y el logotipo está representado por la imagen de dos riñones con una nariz de clown, cuya finalidad será realizar tratamientos de Hemodiálisis con terapia de la risa a pacientes con Enfermedad Renal Crónica Terminal asegurados del Ministerio de Salud, EsSalud y privados, contribuyendo a atender la actual demanda. Los responsables del Centro están conformados por una junta general de accionistas, una gerencia y un directorio. La estrategia del negocio es de liderazgo en costos, centrándonos en el desarrollo de los procesos necesarios para brindar el servicio de hemodiálisis. La Viabilidad Financiera del Proyecto ha sido estructurada de 5 años (2021 – 2025). La inversión total proyectada para el desarrollo del proyecto es de S/.1 287,880.69. El Valor Actual Neto positivo nos indica que el proyecto nos genera beneficios. Por otro lado, nos ofrece una tasa interna de retorno de 176.62%, demostrando que la rentabilidad del proyecto es superior al mínimo aceptable. Por lo descrito el proyecto resulta financieramente viable y rentable. / The business plan belongs to the health sector and consists of the creation of the first Center specialized in Hemodialysis with laughter therapy in the city of Lima. In the Lima region there is an unsatisfied demand for patients with Terminal Chronic Kidney Disease From the Analysis of the kidney situation in Peru (2015) it can be concluded that there is an excess demand for patients in EsSalud, with an oversizing of 33.9 % and a deficit of coverage in the Ministry of Health in 79%. It is important to detail that studies have been seen on the benefits of laughter therapy in patients with Terminal Chronic Diseases and their families regarding their quality of life. For this reason, the creation of the first Center specialized in Hemodialysis with laughter therapy is proposed in the city of Lima called "Center de Hemodialysis NefroClown S.A.". Being the slogan of our center “… Where health begins with a smile”. And the logo is represented by the image of two kidneys with a clown nose, the purpose of which will be to carry out Hemodialysis treatments with laughter therapy to patients with Terminal Chronic Kidney Disease insured by the Ministry of Health, EsSalud and private companies, helping to attend to the current demand. Those responsible for the Center are made up of a general meeting of shareholders, a management and a board of directors. The business strategy is one of cost leadership, focusing on the development of the processes necessary to provide the hemodialysis service. The Financial Viability of the Project has been structured for 5 years (2021 - 2025). The total investment projected for the development of the project is S / .1 287,880.69. The positive Net Present Value indicates that the project generates benefits for us. On the other hand, it offers us an internal rate of return of 176.62%, showing that the profitability of the project is higher than the acceptable minimum. As described, the project is financially viable and profitable. / Trabajo de investigación